Behavioral and biochemical effects of subchronic treatment with (?)3-(3-hydroxyphenyl)-N-n-propylpiperidine in the rat: Dopamine receptor sensitivity and tolerance

Abstract

Male Sprague-Dawley rats were treated for 3 weeks with (-)3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP). Twenty-four hours, but not 72 hours, after withdrawal of the treatment there was an increase in locomotor activity in comparison with saline treated controls. At the same time there was a decrease in striatal DOPAC and HVA and an increased locomotor activity response to apomorphine, indicating supersensitive dopamine receptors. There was no evidence for behavioral tolerance since the suppression of locomotor activity after an acute dose of (-)3-PPP was the same in (-)3-PPP-pretreated as in saline-treated controls. Plasma levels of (-)3-PPP in these animals were, however, slightly decreased.

Sub-chronic administration of (?)-3-PPP and central dopamine receptor sensitivity changes

“…Admittedly, however, the data do not readily allow a clearcut delineation of the relative contribution of the potential DA autoreceptor sub-and postsynaptic receptor supersensitivity to the net behavioural/biochemical effects. For example, although not seen in our experiments, Ahlenius et al (1984) observed a slight elevation of spontaneous motor activity in rats 24 (but not 72) hours after withdrawal from sub-chronic (-)-3-PPP treatment. Such a finding can be explained by either a small reduction in DA autoreceptor sensitivity, a small increase in postsynaptic DA receptor sensitivity, or a combination of both.…”

“…From the present and previous biochemical/behavioural (I-Ijorth et al, 1983) and pharmacokinetic (Ahlenius et al, 1984) findings, the sub-chronic (-)-3-PPP treatment regime applied can be assumed to produce active drug concentrations during approximately a third of the time (i.e. -8 hours out of a 24 hours-period).…”